IL-17A (originally named CTL-8, and also known as IL-17) is the archetypical/founding member of the IL-17 family of cytokines. In addition to IL-17A, members of the IL-17 cytokine family presently include the proteins IL-17B, IL-17C, IL-17D, IL-17E (also called IL-25) and IL-17F that share a conserved C-terminal region but different N-terminal segments.
IL-17A and IL-17F are the two most closely related members of the family, both in terms of sequence and biological properties. IL-17F shares 55% sequence identity with IL-17A at the amino acid level. Both IL-17A and IL-17F are secreted as disulfide linked homodimers which signal through the receptors IL-17R, IL-17RC, or a multimeric receptor complex composed of the IL-17R and IL-17RC. Both are also co-expressed on the same T cell subsets (principally by the Th17 CD4+ T cells).
Moreover, both have been similarly implicated as contributing agents to progression and pathology of a variety of inflammatory and auto-immune diseases in humans and in mouse models of human diseases. Specifically, IL-17A and IL-17F have been implicated as major effector cytokines that trigger inflammatory responses and thereby contribute to a number of autoinflammatory diseases including multiple sclerosis, rheumatoid arthritis, and inflammatory bowel diseases and cancer.
The demonstrated in vivo activities of both IL-17A and IL-17F illustrate the clinical and/or therapeutic potential of, and need for, IL-17A and IL-17F antagonists. Specifically, antibodies that bind to both IL-17A and IL-17F and inhibit (antagonist antibodies) one or more of the immunological activities of both IL-17A and Il-17F would be beneficial. Thus, there remains a need in the art for an antagonist to are cross reactive to both IL-17A and IL-17F and IL-17A/IL-17F heterodimeric complex.